bluebird bio Presents Positive Long-Term Data On LYFGENIA™ (lovotobegligene autotemcel) Gene Therapy for Sickle Cell Disease at 66th American Society of Hematology (ASH) Annual Meeting and Exposition
bluebird bio (BLUE) presented long-term data for LYFGENIA™ gene therapy in sickle cell disease at ASH Annual Meeting. The study included 70 treated patients with up to 9 years of follow-up. Key findings show stable production of anti-sickling adult hemoglobin and significant reduction in vaso-occlusive events across all evaluable patients (n=38).
Notable results include 94.7% of evaluable patients achieving complete resolution of severe VOEs, and 86.8% achieving complete resolution of VOEs. All pediatric patients (10/10) showed complete resolution of VOEs. In patients with stroke history, no recurrence was observed through 9 years of follow-up.
The safety profile aligned with known effects of myeloablative conditioning, with no cases of graft failure or GVHD. However, two patients from an earlier version of the therapy developed acute myeloid leukemia and subsequently died.
bluebird bio (BLUE) ha presentato i dati a lungo termine per la terapia genica LYFGENIA™ nella malattia falciforme all'Assemblea Annuale ASH. Lo studio ha incluso 70 pazienti trattati con un follow-up fino a 9 anni. Risultati chiave mostrano una produzione stabile di emoglobina adulta anti-sickle e una significativa riduzione degli eventi vaso-occlusivi in tutti i pazienti valutabili (n=38).
Risultati notevoli includono il 94,7% dei pazienti valutabili che hanno raggiunto la completa risoluzione di VOE severi, e l'86,8% ha raggiunto la completa risoluzione di VOE. Tutti i pazienti pediatrici (10/10) hanno mostrato una completa risoluzione di VOE. Nei pazienti con una storia di ictus, non si è osservata recidiva nel corso dei 9 anni di follow-up.
Il profilo di sicurezza è allineato agli effetti noti della condizionamento mieloablativo, senza casi di fallimento del trapianto o GVHD. Tuttavia, due pazienti di una versione precedente della terapia hanno sviluppato leucemia mieloide acuta e successivamente sono deceduti.
bluebird bio (BLUE) presentó datos a largo plazo de la terapia génica LYFGENIA™ en la enfermedad de células falciformes en la Reunión Anual ASH. El estudio incluyó a 70 pacientes tratados con seguimiento de hasta 9 años. Hallazgos clave muestran una producción estable de hemoglobina adulta anti-sickling y una reducción significativa de eventos vaso-oclusivos en todos los pacientes evaluables (n=38).
Resultados notables incluyen el 94.7% de los pacientes evaluables alcanzando resolución completa de VOEs severos, y el 86.8% alcanzando resolución completa de VOEs. Todos los pacientes pediátricos (10/10) mostraron resolución completa de VOEs. En pacientes con antecedentes de accidente cerebrovascular, no se observó recurrencia a lo largo de 9 años de seguimiento.
El perfil de seguridad se alineó con los efectos conocidos del acondicionamiento mieloablativo, sin casos de falla del injerto o GVHD. Sin embargo, dos pacientes de una versión anterior de la terapia desarrollaron leucemia mieloide aguda y posteriormente fallecieron.
bluebird bio (BLUE)는 ASH 연례 회의에서 겸형 적혈구병에 대한 LYFGENIA™ 유전자 치료의 장기 데이터를 발표했습니다. 이 연구에는 최대 9년의 추적 관찰을 받은 70명의 치료 환자가 포함되었습니다. 주요 발견은 모든 평가 가능한 환자(n=38)에서 항 겸형 적혈구 성인 헤모글로빈의 안정적인 생산과 혈관 폐쇄 사건의 유의미한 감소를 보여줍니다.
주목할 만한 결과로는 94.7%의 평가 가능한 환자가 심각한 VOE의 완전한 해소를 달성했으며, 86.8%는 VOE의 완전한 해소를 달성했습니다. 모든 소아 환자(10/10)는 VOE의 완전한 해소를 보여주었습니다. 뇌졸중 병력이 있는 환자에서는 9년의 추적 관찰 기간 동안 재발이 관찰되지 않았습니다.
안전성 프로필은 알려진 골수 제거 조건의 효과와 일치하며, 이식 실패나 GVHD의 사례가 없었습니다. 그러나 이전 버전의 치료를 받은 환자 중 두 명이 급성 골수성 백혈병을 개발하고 이후 사망했습니다.
bluebird bio (BLUE) a présenté des données à long terme sur la thérapie génique LYFGENIA™ dans la drépanocytose lors de la réunion annuelle de l'ASH. L'étude comprenait 70 patients traités avec jusqu'à 9 ans de suivi. Résultats clés montrent une production stable d'hémoglobine adulte anti-sickle et une réduction significative des événements vaso-occlusifs chez tous les patients évaluables (n=38).
Les résultats notables incluent 94,7 % des patients évaluables ayant atteint une résolution complète des VOE sévères, et 86,8 % atteignant une résolution complète des VOE. Tous les patients pédiatriques (10/10) ont montré une résolution complète des VOE. Chez les patients ayant des antécédents d'accident vasculaire cérébral, aucune récidive n'a été observée au cours des 9 années de suivi.
Le profil de sécurité était conforme aux effets connus du conditionnement myéloablatif, sans cas d'échec de greffe ni de GVHD. Cependant, deux patients d'une version antérieure de la thérapie ont développé une leucémie myéloïde aiguë et sont décédés par la suite.
bluebird bio (BLUE) hat auf dem ASH-Jahrestreffen Langzeitdaten zur LYFGENIA™-Gentherapie bei der Sichelzellenkrankheit vorgestellt. Die Studie umfasste 70 behandelte Patienten mit einer Nachbeobachtungszeit von bis zu 9 Jahren. Wichtige Ergebnisse zeigen eine stabile Produktion von anti-sickle erwachsener Hämoglobin und eine signifikante Reduzierung von vaso-okkulsiven Ereignissen bei allen evaluierten Patienten (n=38).
Bemerkenswerte Ergebnisse sind, dass 94,7 % der evaluierten Patienten eine vollständige Auflösung schwerer VOEs erreicht haben, und 86,8 % eine vollständige Auflösung von VOEs erreichten. Alle pädiatrischen Patienten (10/10) zeigten eine vollständige Auflösung von VOEs. Bei Patienten mit Schlaganfallgeschichte wurde über die 9 Jahre Nachbeobachtungszeit kein Rückfall beobachtet.
Das Sicherheitsprofil stimmte mit den bekannten Auswirkungen der myeloablativen Konditionierung überein, es gab keine Fälle von Transplantationsversagen oder GVHD. Allerdings entwickelten zwei Patienten aus einer früheren Version der Therapie eine akute myeloische Leukämie und starben anschließend.
- 94.7% of evaluable patients achieved complete resolution of severe VOEs
- 86.8% of evaluable patients achieved complete resolution of VOEs
- 100% success rate in pediatric patients (10/10) for VOE resolution
- No stroke recurrence in patients with prior history through 9 years of follow-up
- Stable hemoglobin production maintained (median >40% HbAT87Q)
- Two patient deaths from acute myeloid leukemia in earlier version of therapy
Insights
The long-term data presented for LYFGENIA demonstrates remarkable clinical efficacy with 94.7% of evaluable patients achieving complete resolution of severe vaso-occlusive events and 86.8% achieving complete resolution of all VOEs. The durability of response, with a median follow-up of 47.7 months, strongly supports the therapy's transformative potential.
Particularly groundbreaking is the stroke prevention data - no recurrence of strokes in patients with prior stroke history through 9 years of follow-up. This is clinically significant given that traditional treatments like transfusions offer only modest protection against secondary strokes. The 100% response rate in pediatric patients further validates the therapy's robust efficacy profile.
This data significantly strengthens LYFGENIA's commercial position as the most extensively studied gene therapy for sickle cell disease. With 70 patients treated and up to 9 years of follow-up data, the robust efficacy and safety profile should support market adoption and payer coverage. The positive outcomes in high-risk stroke patients represent a key differentiator from competing therapies.
For bluebird bio, with a market cap of just
Stable production of anti-sickling adult hemoglobin (HBAT87Q) and elimination or significant reduction of vaso-occlusive events sustained through last follow-up for all evaluable patients (n=38), underscoring potentially transformative and durable clinical impact
Results from first and only focused analysis of patients with sickle cell disease with a history of overt or silent stroke (n=27) show no stroke recurrence through 9 years of follow-up (n=2)
“Data presented at ASH demonstrate that the potentially transformative benefits of LYFGENIA are sustained through additional long-term follow-up and consistent across sub-populations, including patients with overt stroke, not studied in any other clinical development program of gene therapy for sickle cell disease.” said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “These data continue to distinguish LYFGENIA as the most deeply studied gene therapy for sickle cell disease, with the most patients treated, longest follow-up, and broadest range of clinical presentations evaluated across the field.”
Updated efficacy data continue to support sustained, transformational impact on VOE burden and hematologic markers of disease
An update on clinical response to lovo-cel in patients living with sickle cell disease focused on 58 patients who received lovo-cel in the HGB-206 Group C (n=36) and HGB-210 (n=22) studies, following enhancements to the manufacturing and treatment protocols, will be presented in Oral Presentation #511: An Update on Lovotibeglogene Autotemcel (lovo-cel) Clinical Trials for Sickle Cell Disease (SCD) and Analysis of Early Predictors of Response to Lovo-cel. Median follow-up time was 47.7 months (4.0 years), with 15 study participants having 5 or more years of follow-up.
Stacy Rifkin-Zenenberg, DO, Hackensack Meridian Health said: “These data demonstrate that the significant clinical benefits of lovo-cel for people living with sickle cell disease are durable through continued long-term follow-up. Additionally, the number of patients treated, and duration of follow-up, has enabled detailed exploration of the pharmacology and mechanism of action of LVV gene therapy for sickle cell disease, providing even greater support that one-time treatment with lovo-cel has the potential to permanently address the underlying cause of sickle cell disease.”
As of the July 2024 cutoff date, all patients continued to have stable production of anti-sickling adult hemoglobin after infusion through last follow-up (median >
VOEs and severe vaso-occlusive events (sVOEs) were eliminated or significantly reduced in all patients. Specific findings include:
-
36/38 (
94.7% ) of evaluable patients achieved complete resolution of severe VOEs (sVOE-CR) in the 6-18 months post infusion, maintained for a median (min, max) of 42.3 months (12.2, 70.5). -
33/38 (
86.8% ) of evaluable patients achieved complete resolution of VOEs (VOE-CR), maintained for a median (min, max) of 42.4 (12.2, 70.5) months. -
10/10 (
100% ) pediatric patients achieved complete resolution of VOEs and sVOEs.
The safety profile of the lovo-cel treatment regimen was generally consistent with underlying sickle cell disease and the known effects of myeloablative conditioning. There were no cases of graft failure or graft-versus-host disease (GVHD), no vector-related complications, and no insertional oncogenesis. For complete safety information please refer to the
Data from patients with sickle cell disease and a history of overt stroke show no recurrence of stroke following treatment with lovo-cel
The first focused analysis of the clinical impact of lovo-cel on patients with sickle cell disease with a history of stroke, including overt stroke, will be presented in Poster Presentation #3576: Participants with a History of Stroke in Lovotibeglogene Autotemcel (lovo-cel) Clinical Trials.
Data showed that patients with a history of overt stroke remained stable without recurrent stroke up to 9 years post-treatment (n=6), with median follow-up of 6.5 years.
Jennifer Jaroscak, MD, Director, Pediatric Non-Malignant Transplant, Medical University of
Overt ischemic stroke is a devastating complication of sickle cell disease and requires lifelong chronic transfusions or allogeneic hematopoietic stem cell transplantation, which carry significant risk of complications. One in four patients living with sickle cell disease have a stroke by age 45.
Other clinical outcomes in patients with a history of stroke—including expression of gene therapy derived anti-sickling hemoglobin (HBAT87Q), improvements in total hemoglobin, and impact on other hematologic markers—were consistent with those patients’ respective study populations (HGB-206 Group A and HGB-206 Group C).
The analysis also included 21 patients who had evidence of silent stroke based on available MRI data at screening. In this cohort there were no reports of recurrent overt or silent stroke among patients with follow-up MRIs, with a median 3.5 years follow-up (.48, 6.88 years).
Silent ischemic stroke adversely affects neurocognitive function and is associated with increased risk of overt stroke. It occurs in an estimated
Safety findings for participants with a history of overt stroke did not differ from that in the overall treatment group. No increase in hypertension, bleeding issues, prolonged thrombocytopenia or catheter-related thromboses were observed. As previously reported, cases of acute myeloid leukemia were observed in two patients from the HGB-206 Group A cohort who were treated with an earlier version of the therapy prior to enhancements to the treatment and manufacturing processes. Both patients died due to aforementioned leukemia.
About LYFGENIA™ (lovotibeglogene autotemcel) or lovo-cel
LYFGENIA is a one-time ex-vivo lentiviral vector gene therapy approved for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events (VOEs). LYFGENIA works by adding a functional β-globin gene to patients’ own hematopoietic (blood) stem and progenitor cells (HSPCs). Durable production of adult hemoglobin with anti-sickling properties (HbAT87Q) is possible following successful engraftment. HbAT87Q has a similar oxygen-binding affinity to wild-type HbA, limits sickling of red blood cells and has the potential to reduce VOEs. The Phase 1/2 HGB-206 study of LYFGENIA is complete and the Phase 3 HGB-210 study evaluating LYFGENIA is ongoing. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for patients with sickle cell disease who have been treated with LYFGENIA in bluebird bio-sponsored clinical studies.
Indication
LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events (VOEs).
Limitations of Use
Following treatment with LYFGENIA, patients with α-thalassemia trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions. LYFGENIA has not been studied in patients with more than two α-globin gene deletions.
Important Safety Information
Boxed WARNING: HEMATOLOGIC MALIGNANCY
Hematologic malignancy has occurred in patients treated with LYFGENIA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through integration site analysis at Months 6, 12, and as warranted.
Hematologic Malignancy
Hematologic malignancy has occurred in patients treated with LYFGENIA (Study 1, Group A). At the time of initial product approval, two patients treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A) developed acute myeloid leukemia (AML). One patient with α-thalassemia trait (Study 1, Group C) has been diagnosed with myelodysplastic syndrome (MDS).
The additional hematopoietic stress associated with mobilization, conditioning, and infusion of LYFGENIA, including the need to regenerate the hematopoietic system, may increase the risk of a hematologic malignancy. Patients with sickle cell disease have an increased risk of hematologic malignancy as compared to the general population.
Patients treated with LYFGENIA may develop hematologic malignancies and should have lifelong monitoring. Monitor for hematologic malignancies with a complete blood count (with differential) at least every 6 months for at least 15 years after treatment with LYFGENIA, and integration site analysis at Months 6, 12, and as warranted.
In the event that a malignancy occurs, contact bluebird bio at 1-833-999-6378 for reporting and to obtain instructions on collection of samples for testing.
Post-Marketing Long Term Follow-Up Study: Patients who intend to receive treatment with LYFGENIA are encouraged to enroll in the study, as available, to assess the long-term safety of LYFGENIA and the risk of malignancies occurring after treatment with LYFGENIA by calling bluebird bio at 1-833-999-6378. The study includes monitoring (at pre-specified intervals) for clonal expansion.
Delayed Platelet Engraftment
Delayed platelet engraftment has been observed with LYFGENIA. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia. Two patients (
Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise.
Neutrophil Engraftment Failure
There is a potential risk of neutrophil engraftment failure after treatment with LYFGENIA. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 0.5 × 109 cells/L obtained on different days by Day 43 after infusion of LYFGENIA. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with LYFGENIA, provide rescue treatment with the back-up collection of CD34+ cells.
Insertional Oncogenesis
There is a potential risk of lentiviral vector-mediated insertional oncogenesis after treatment with LYFGENIA.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of LYFGENIA. The dimethyl sulfoxide (DMSO) or dextran 40 in LYFGENIA may cause hypersensitivity reactions, including anaphylaxis.
Anti-retroviral Use
Patients should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization and until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.
Hydroxyurea Use
Patients should not take hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed. If hydroxyurea is administered between mobilization and conditioning, discontinue 2 days prior to initiation of conditioning.
Iron Chelation
Drug-drug interactions between iron chelators and the mobilization process and myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of mobilization or conditioning. Do not administer myelosuppressive iron chelators (e.g., deferiprone) for 6 months post-treatment with LYFGENIA. Non-myelosuppressive iron chelation should be restarted no sooner than 3 months after LYFGENIA infusion. Phlebotomy can be used in lieu of iron chelation, when appropriate.
Interference with PCR-based Testing
Patients who have received LYFGENIA are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a possible false-positive PCR assay test result for HIV. Therefore, patients who have received LYFGENIA should not be screened for HIV infection using a PCR-based assay.
Adverse Reactions
The most common adverse reactions ≥ Grade 3 (incidence ≥
Pregnancy/Lactation
Advise patients of the risks associated with myeloablative conditioning agents, including on pregnancy and fertility.
LYFGENIA should not be administered to women who are pregnant, and pregnancy after LYFGENIA infusion should be discussed with the treating physician.
LYFGENIA is not recommended for women who are breastfeeding, and breastfeeding after LYFGENIA infusion should be discussed with the treating physician.
Females and Males of Reproductive Potential
A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before LYFGENIA administration.
Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra-uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of LYFGENIA.
Advise patients of the options for fertility preservation.
Please see full Prescribing Information for LYFGENIA including Boxed WARNING and Medication Guide.
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days.
Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers.
With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward.
bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding the therapeutic potential of LYFGENIA. Such forward-looking statements are based on historical performance and current expectations and projections about bluebird’s future goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond bluebird’s control and could cause bluebird’s future goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC. These risks and uncertainties include, but are not limited to: the risk that the efficacy and safety results from bluebird’s prior and ongoing clinical trials will not continue or be seen in the commercial context; the risk that there is not sufficient patient demand or payer reimbursement to support continued commercialization of LYFGENIA; the risk of insertional oncogenic or other safety events associated with lentiviral vector, drug product, or myeloablation, including the risk of hematologic malignancy; and the risk that bluebird’s products, including LYFGENIA, will not be successfully commercialized. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, bluebird bio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
View source version on businesswire.com: https://www.businesswire.com/news/home/20241208134842/en/
Investors:
Courtney O’Leary, 978-621-7347
coleary@bluebirdbio.com
Media:
Jess Rowlands, 857-299-6103
jess.rowlands@bluebirdbio.com
Source: bluebird bio, Inc.
FAQ
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